This project is concerned with elucidation of the cellular and molecular mechanisms of cytotoxic proteins from two marine invertebrates, the nemertine Cerebratulus and the sea anemone Stoichactis. Analysis of the interactions of these toxins with membranes should improve our knowledge of lipid-protein interactions and determine whether cytotoxic proteins exploit different modes of interaction with lipid bilayers than do intrinsic membrane proteins. Both Cerebratulus and Stoichactic cytotoxins preferentially interacted with sphingomyelin; the former toxin also interacts with gangliosides. Erythrocytes from various mammalian species showed considerable variations in sensitivity to the toxins. Spectroscopic, electrophysiological, sequencing, and isotopic binding methods are being used to investigate the modes of interaction of the toxins with cellular and liposomal membranes.